Vitamin K biosynthesis and the human gut microbiota.
Karl, James.
2015
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Abstract: Emerging
evidence suggests novel physiologic functions for vitamin K beyond the vitamin's
canonical role in hemostasis. Mechanisms underlying these functions are not well
characterized, though several are thought to be independent of vitamin K-dependent
protein activity and unique to bacterially-synthesized forms of vitamin K known as
menaquinones (MKn). Many gut bacteria synthesize ... read moreMKn, making the human gut a potential
source of vitamin K, and factors influencing gut bacteria community composition possible
mediators of vitamin K nutriture. However, the contribution of bacterially-synthesized
MKn to human vitamin K nutriture is uncertain due, in part, to an incomplete
characterization of gut MKn content and of the gut bacteria that synthesize MKn.
Moreover, the dietary and non-dietary factors influencing gut bacteria MKn production
have not been elucidated. The objective of this research was to leverage recent
technological advancements in microbial ecology, bioinformatics and analytical chemistry
to characterize gut MKn content, identify associated gut bacteria, and examine effects
of diet-mediated changes in gut bacteria community composition on gut MKn content. To
meet this objective, a sensitive, selective and high-throughput liquid
chromatography-mass spectrometry method for quantifying vitamin K in feces, food and
serum was developed and validated. This assay was then utilized to measure fecal vitamin
K content in individuals participating in two separate diet interventions investigating
the effects of whole grain-based diets on gut bacteria community composition and
cardiometabolic health. Collectively, the findings demonstrate that fecal MKn
concentrations would exceed the dietary vitamin K requirement if fully absorbed, and are
characterized by substantial inter-individual variability in both the quantity and forms
of MKn present. Further, gut bacteria community composition appears to explain this
variability, and diet modifications that alter gut bacteria community composition
measurably impact fecal MKn content. MKn were not detectable in circulation, challenging
recent, controversial reports that MKn synthesized by gut bacteria are present in
circulation at concentrations within the detectable limits of current assays.
Cross-sectional associations between fecal vitamin K content and several biomarkers of
cardiometabolic health were observed, and are hypothesis-generating. However, the
associations are limited by small sample sizes and were not confirmed in longitudinal
analysis. As such, the relevance of these findings to human health is unclear, but
merits further investigation. The analytic tools developed and gut bacteria-MKn
interrelationships demonstrated as part of this research provide a foundation for those
investigations .
Thesis (Ph.D.)--Tufts University, 2015.
Submitted to the Dept. of Biochemical and Molecular Nutrition.
Advisor: Sarah Booth.
Committee: Edward Saltzman, Susan Roberts, and Liping Zhao.
Keyword: Nutrition.read less - ID:
- 9k41zr85q
- Component ID:
- tufts:20389
- To Cite:
- TARC Citation Guide EndNote
